How Military Research On Anthrax Could Lead To A Weapon Against Gluten

Students at the University of Washington used a protein-folding program initially funded by the Defense Advanced Research Projects Agency to come up with a treatment for celiac disease.

DARPA

Originally published on January 14, 2013 8:06 am

Why would the Defense Advanced Research Projects Agency — the people who helped bring the world stealth fighters and GPS — fund research into man-made proteins that could make it easier for some Americans to eat pizza?

That's what we wondered when we read that the Pentagon's gee-whiz research arm provided support for work on a drug to treat celiac disease, a condition that interferes with the digestion of gluten in wheat and other foods.

So we asked.

Mildred Donlon, a DARPA program manager, told Shots the agency has no interest in developing a treatment for celiac disease.

But in a strange twist of scientific fate, student researchers tried to crack the celiac puzzle with tools developed with DARPA funding.

How did it happen? Between 2005 and 2009, DARPA invested in computerized methods to find medical defenses for chemical and biological warfare threats like Sarin nerve gas and anthrax.

Now deadly anthrax spores and gluten are certainly threats on a very different scale, but researchers believe they both could be vulnerable to carefully designed enzymes. DARPA funded computerized techniques to develop better enyzmes faster.

Designing proteins, including enzymes, is the raison d'etre of David Baker's biochemistry lab at the University of Washington in Seattle. The lab used some DARPA money to fund its work, including development of a program called FoldIt, which enlists researchers (and citizen scientists) to figure out which among many possible protein structures is the best one to solve certain biomedical problems.

According to researchers who published a paper last month in the Journal of the American Chemical Society, a group of undergraduates at UW used FoldIt to come up with an enzyme that could break down gluten in the stomach.

The idea is to develop an enzyme pill that would eliminate gluten before it triggers a damaging immune response in people with celiac disease and to help people with the condition absorb nutrients better.

Nearly 1 in 133 Americans suffers from celiac disease, according to the University of Maryland Center for Celiac Research in Baltimore. But currently the only treatment is a gluten-free diet, which can be difficult for many people to stick with.

So there's likely a market for a pill they could take with meals the way people with lactose intolerance can take the enzyme lactase before consuming dairy products.

"The idea is you would pop your pill and then drink your beer, eat your pizza and cookies, and be quite happy," says Justin Siegel, an assistant professor of biochemistry and molecular medicine at the University of California, Davis and an author of the paper.

According to Ingrid Swanson Pultz, a microbiologist at University of Washington and another author of the paper, the students found an enzyme that could withstand stomach acids. They then tweaked it to go after gluten.

It worked so well in the test tube that Siegel and Pultz have founded a company, Proteus Biologics, to try and bring it to market.

Siegel says they'll need to show in a clinical test that the protein can degrade enough gluten fast enough in the complex environment of the gut to be useful to people with celiac disease. They'll also have to prove that it doesn't have any toxic effects when eaten.

But don't expect an anti-gluten drug on the market anytime soon – even if Siegel and the other researchers decide to market it as a supplement (like a lactase pill), which would require far fewer trials than a drug. It could still take years to prove it's safe.